Le délai optimal entre une lésion médullaire traumatique (LMT) et la chirurgie demeure indéterminé. Cependant, la relation entre la prévention de complications et le délai chirurgical n’a jamais été spécifiquement étudiée. L’objectif principal de ce travail était de détecter si les taux de complications chez des LMT étaient associés avec le délai chirurgical. L’objectif secondaire était d’identifier si le délai chirurgical est un prédicteur indépendant de la survenue de complications. Un premier article présente l’analyse d’une cohorte rétrospective de 431 LMTs. Une chirurgie réalisée dans un délai inférieur à 24h (ou inférieur à 72h si un délai de 24h ne peut être respecté) prédisait une diminution du taux de l’ensemble des complications, du taux de pneumonies et du taux de plaies de pression. Les autres facteurs prédictifs de complications identifiés étaient : l’âge, la sévérité de l’atteinte neurologique de la lésion selon l’échelle ASIA, un traumatisme cervical plutôt que thoracique, la présence de comorbidités, la sévérité du traumatisme selon l’échelle ISS et la complexité de la chirurgie. Les connaissances actuelles suggèrent qu’une opération chirurgicale rapide n’a que peu d’effet sur la récupération neurologique chez les LMTs complètes (interruption complète des fonctions sensorimotrices). Pour cette raison, notre second article analyse l’impact du délai chirurgical sur la survenue des complications à partir d’une sous-population de 197 LMTs complètes de notre cohorte. Un délai chirurgical supérieur à 24h prédisait une augmentation des complications, notamment les pneumonies et les infections urinaires. Bien que des études prospectives randomisées sont nécessaires pour confirmer nos conclusions, nos études supportent un délai chirurgical rapide afin de diminuer le taux de complications non neurologiques chez les LMTs. / Optimal timing of surgery after traumatic spinal cord injury (SCI) is one of the most controversial subjects in spine surgery. However, the relationship between prevention of peri-operative complications and timing of surgical decompression was never specifically studied. The primary goal of our study was to evaluate if the peri-operative complication rate was associated with surgical timing. The secondary goal of our study was to identify if surgical timing is an independent predictor of complications. A first publication presents the analysis of a retrospective cohort of 431 cases of traumatic SCI. A reduction in the global rate of complications as well as the incidence of pneumonia and pressure ulcer were predicted by surgery performed earlier than 24 hours (or earlier than 72 hours if the surgery could not be performed within 24 hours following the SCI). Other predictors where statistically related to the occurrence of complications: increasing age, severity of neurological injury, a cervical rather than a thoracic lesion, medical comorbidities, the severity of trauma, and the complexity of surgery. Previous studies suggest that early surgery is of little benefit for neurological recovery in complete traumatic SCI (with complete interruption of sensorimotor function). Therefore our second publication analyzed the impact of early surgical intervention in the sub-population of 197 complete SCI. Surgical timing later than 24 h was a predictor of complications, specifically pneumonia and UTI. Although a randomized controlled trial is needed to confirm our findings, our studies support that early surgical timing after traumatic SCI (typically within 24 hours) could decrease the rate of non neurological complications.

L'insuffisance rénale chronique (IRC) se caractérise par la diminution progressive et irréversible des fonctions renales. Elle s'accompagne d'une accumulation d'un ensemble de toxines responsable du syndrome urémique. Le syndrome urémique touche tous les organes, et de façon préoccupante le système cardiovasculaire. Il est associé à une dysfonction endothéliale, à la production d'un stress oxydant et d'une inflammation. L'objectif de cette thèse était d'identifier les mécanismes moléculaires responsables des complications du syndrome urémique. La première partie a tenté d'identifier des épissages alternatifs associés à l'IRC. Deux épissages alternatifs ont été identifiés. Cependant, le petit nombre d'épissages alternatifs trouvé au vue du nombre de gènes étudiés, nous permet de conclure que si l'IRC peut être responsable de l'apparition d'épissages alternatifs, ce phénomène n'est pas déterminant dans la régulation de l'expression des gènes responsable des complications de l'IRC. Dans la deuxième partie, nous avons montré par une étude clinique que le taux d'une toxine urémique, l'acide indole acétique (IAA), était associé à la mortalité et à la survenue d'événements cardio-vasculaires. In vitro, l'IAA induit un stress oxydant et un signal inflammatoire par l'induction de la cyclooxygénase 2 (COX-2). Une voie inflammatoire non génomique impliquant aryl hydrocarbon receptor (AhR), p38 MAPK et NF-κB est responsable de l'induction de la COX-2 endothéliale par l'IAA. Nos travaux ont identifié de nouvelles cibles thérapeutiques dont la modulation pourrait avoir un impact sur la mortalité cardiovasculaire des patients présentant une maladie rénale chronique. / Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney functions. Accumulation of uremic toxins is implicated in the uremic syndrome. Uremic syndrome affects all organs and particularly the cardiovascular system. The aim of this thesis was to identify and understand the molecular mechanisms implicated in the uremic syndrome.The first part attempted to ascertain the existence of alternative splice events associated with CKD. Two alternative splicing were identified. The small number of alternative splice events highlighted allows us to conclude that this phenomenon does not seem to be a key event in the modulation of gene expression during CKD.In the second part of this work, we demonstrated that the plasmatic concentration of an uremic toxin, Indole-3-acetic acid (IAA), is associated with all-cause mortality and major cardiovascular events. In vitro, we demonstrated that IAA induced endothelial cyclooxygenase-2 expression and endothelial oxidative stress production. IAA activated an endothelial Aryl hydrocarbon receptor/P38MAPK/NF-κB pathway. The activation of this inflammatory AHR dependant pathway could play a critical role in the increase of cardiovascular morbidity and mortality observed during CKD.Our work provides new therapeutic targets. The modulation of their activation could reduce cardiovascular mortality in patients with chronic kidney disease.

Introdução: Nos indivíduos diabéticos com sintomas do trato urinário inferior e aumento prostático, é imprescindível distinguir se os sintomas provêm de obstrução infravesical provocada pelo aumento da próstata, ou de alterações funcionais da bexiga, decorrentes de distúrbios neurogênicos, uma vez que estas doenças podem apresentar os mesmos sintomas. A importância do diagnóstico baseia-se no fato de que ambas possuem modalidades de tratamentos diferentes e específicos, considerando-se que nem todos os pacientes com estes sintomas apresentam melhora após o tratamento cirúrgico. Objetivos: O presente estudo tem por objetivos: determinar a prevalência da obstrução infravesical em pacientes diabéticos, com sintomas do trato urinário inferior e hiperplasia prostática benigna, e analisar o valor preditivo para obstrução infravesical dos métodos de avaliação menos invasivos, como: o escore internacional de sintomas prostáticos, fluxometria, resíduo pós-miccional e volume prostático nesses indivíduos. Casuística e Métodos: Cinqüenta pacientes foram selecionados e avaliados clinicamente, submetendo-se ao escore internacional de sintomas prostáticos, exames laboratoriais de imagens e estudo urodinâmico. Realizou-se avaliação urodinâmica para diagnóstico de obstrução infravesical, fundamentando-se nos critérios da Sociedade Internacional de Continência. Nos casos duvidosos, utilizou-se o nomograma de Schäfer para classificar os pacientes como obstruídos ou não. Resultados: O diagnóstico de obstrução infravesical foi realizado através do estudo pressão/fluxo, o qual classificou 24 pacientes (48%) como obstruídos e 26 (52%) como não obstruídos, onde os sintomas poderiam decorrer de cistopatia diabética. O escore internacional dos sintomas prostáticos não se correlacionou com obstrução infravesical documentada pela urodinâmica, demonstrando não ser bom parâmetro para o seu diagnóstico. O volume prostático foi maior nos pacientes obstruídos. O resíduo pós-miccional foi semelhante em ambos os grupos. A fluxometria nessa população teve baixo valor preditivo, pois o índice de hipocontratilidade vesical teve alta prevalência nesses indivíduos. Conclusão: A avaliação urodinâmica justifica-se como obrigatória em pacientes com sintomas do trato urinário inferior, aumento prostático e Diabetes mellitus, uma vez que medidas menos invasivas - como: o escore internacional de sintomas prostáticos, fluxometria, mensuração do resíduo urinário e do volume prostático -, não têm sensibilidade nem especificidade adequadas para o diagnóstico de obstrução infravesical. A indicação de cirurgia de forma aleatória, neste grupo, pode levar a um alto índice de insucesso. Somente o estudo urodinâmico apresenta sensibilidade e especificidade adequadas para o diagnóstico de obstrução infravesical nesta população. Seu custo, grau de invasibilidade e morbidade são pequenos quando comparados aos de uma cirurgia desnecessária, justificando sua indicação nestes casos. / Introduction: In diabetics with lower urinary tract symptoms and prostatic hypertrophy it is extremely important to distinguish whether these symptoms come from bladder outlet obstruction due to the increasing of the prostate or from bladder dysfunctions due to the neurogenic disturbs, because these pathologies can present the same symptoms. The importance of the diagnosis is due to the fact that both have different and specific form of treatments, believing that not all patients with these symptoms present improvement after surgery. Aims: This study presents the scope to know the bladder outlet obstruction prevalence in the diabetic patients with lower urinary tract symptoms and benign prostatic enlargement and the analysis of the predictive value to bladder outlet obstruction in relationship to the less invasive methods such as: international score of prostatic symptoms, uroflowmetry, residual urine and prostatic volume in these patients. Methods: Fifty patients have been selected and clinically evaluated using the international score of prostatic symptoms, laboratory exams, images and urodynamic study. Urodynamic evaluation was done to the diagnosis of bladder outlet obstruction, following the criteria of the International Continence Society. In doubtful cases, the Shaffer nomogram was used to classify the patients with obstruction or not. Results: The bladder outlet obstruction diagnose was done by the pressure/flow study, which 24 (48%) of the obstructed patients and 26 (52%) no obstructed have been classified, and the symptoms were probably due to the diabetic cistopathy. The international score of prostatic symptoms were not correlated with bladder outlet obstruction showed by urodynamic. The prostatic volume was greater in the obstructed patients. The residual urine was almost the same in both groups. The flowmetry in these cases had the predictive value lower, because the detrusor underactivity had high prevalence in these patients. Conclusions: The urodynamic evaluation is mandatory in the patients with lower urinary tract symptoms, prostatic enlargement and diabetes mellitus once the less invasive measurements as: international score of prostatic symptoms, uroflowmetry, residual urine measurement and prostatic volume, have not the adequate sensitivity and specificity for the bladder outlet obstruction diagnose. The indication for surgery without criteria in this group of patients can lead to a high level of bad results. Only the urodynamic study can present adequate sensitivity and specificity for the bladder outlet obstruction diagnose in such cases. Its cost, invasion degree and morbidity are smaller if you compare it to the unnecessary surgery. So, it is worthwhile to do the urodynamic study in these cases.

OBJETIVO: Analisar a associação entre o estado nutricional materno em gestações de alto risco e complicações do parto, do puerpério e análise do consumo dietético dessas gestantes. MÉTODOS: Estudo prospectivo e observacional realizado no período de agosto de 2009 a agosto de 2010, com os seguintes critérios de inclusão: puérperas até o quinto dia; idade acima de 18 anos; gestação de alto risco; feto único e vivo no início do trabalho de parto; parto na Instituição; peso materno aferido no dia do parto. O estado nutricional no final da gestação foi avaliado pelo índice de massa corporal (IMC), aplicando-se a curva de Atalah. As pacientes foram classificadas em: baixo peso, adequado, sobrepeso e obesidade. O consumo dietético foi avaliado por aplicação do questionário de frequência do consumo alimentar. As complicações do parto e do puerpério, investigadas durante o período de internação e 30 dias após a alta, foram: tipo de parto, infecção e/ou secreção em ferida cirúrgica, infecção urinária, infecção puerperal, febre, hospitalização, uso de antibióticos e morbidade composta (pelo menos uma das complicações puerperais citadas). RESULTADOS: Foram incluídas 374 puérperas classificadas pelo IMC final em: baixo peso (n=54, 14,4%); adequado (n=126, 33,7%); sobrepeso (n=105, 28,1%) e obesidade (n=89, 23,8%). Não houve diferença significativa na proporção de cesáreas quando comparados os seguintes grupos: baixo peso e adequado (68,3%), sobrepeso (76,2%) e obesidade (78,6%, P=0,201). A obesidade materna apresentou associação significativa com as seguintes complicações do puerpério: infecção de ferida cirúrgica (16,7%, P=0,042), infecção urinária (9,0%, P=0,004), uso de antibiótico (12,3%, P<0,001) e morbidade composta (25,6%, P=0,016). Aplicando-se o modelo de regressão logística, verificou-se que a obesidade no final da gestação é variável independente na predição da morbidade composta (OR: 2,09; IC95%: 1,15 - 3,80, P=0,015). A análise do consumo dietético demonstrou média de consumo energético semelhante nos grupos: baixo peso e adequado (2344 cal/dia), sobrepeso (2433 cal/dia) e obesidade (2450 cal/dia, P=0,640). Não se constatou diferença significativa no consumo médio diário de macro e micronutrientes entre os grupos estudados. CONCLUSÃO: A obesidade materna no final da gravidez, em pacientes de alto risco, está associada, de forma independente, com a ocorrência de complicações infecciosas no puerpério, demonstrando a necessidade de acompanhamento mais eficiente em relação ao ganho de peso materno nessas gestações / OBJECTIVE: To assess the association between maternal obesity and the occurrence of delivery and postpartum complications in high risk pregnancies, and to analyze the dietary intake of these pregnant women. METHODS: Prospective and observational study conducted from August 2009 to August 2010, with the following inclusion criteria: admission to the 5th day, maternal age 18-year-old, high-risk pregnancy, single pregnancy, fetus alive at the beginning of labor, birth at the institution, maternal weight measured at birth. Nutritional status in late pregnancy was assessed by body mass index (BMI), and applying the curve Atalah. The patients were classified as: underweight, appropriate, overweight and obesity. The dietary intake was evaluated applying a food frequency questionnaire. The complications of delivery and postpartum, investigated during the hospitalization and 30 days after discharge, were: infection and / or secretion in the surgical wound, urinary tract infection, puerperal infection, fever, hospitalization, antibiotics, and composite morbidity (at least one puerperal complication). RESULTS: We included 374 postpartum women classified by the final BMI: underweight (n=54, 14.4%), appropriate (n=126, 33.7%), overweight (n=105, 28.1%) and obesity (n=89, 23.8%). There was no significant difference in the proportion of cesarean when compared the following groups: underweight and appropriate (68.3%), overweight (76.2%) and obesity (78.6%, P=0.201). Maternal obesity was significantly associated with the following puerperal complications: surgical wound infection (16.8%, P=0.042), urinary tract infection (9.0%, P= 0.004), antibiotic use (12.3%, P<0.001) and composite morbidity (25.6%, P=0.016). The logistic regression model showed that obesity in late pregnancy is an independent variable in predicting the composite morbidity (OR: 2.09, 95% CI: 1.15 to 3.80, P=0.015). The analysis of dietary intake showed average energy consumption similar in the groups: underweight and appropriate (2344 cal/day), overweight (2433 cal/day) and obesity (2450 cal/day, P=0.640). There was no significant difference in the average daily consumption of macro-and micronutrients among the groups studied. CONCLUSION: Maternal obesity at the end of high-risk pregnancy is independently associated with the occurrence of postpartum infectious complications, showing the need for more efficient monitoring of maternal weight gain in these pregnancies

INTRODUÇÃO: O transplante hepático é a terapêutica de escolha para pacientes com hepatopatias avançadas. Melhorias na seleção dos pacientes, avanços cirúrgicos e imunológicos aumentaram a sobrevida. As complicações biliares ocorrem em 15 a 35% dos transplantes e estão associadas a técnicas de redução hepática. A estenose anastomótica ocorre de 5 a 34% e pode ser tratada por cirurgia, acesso endoscópico ou percutâneo. Esse último apresenta bons resultados, mas carece de padronização, critérios de sucesso ou consenso quanto aos fatores que influenciam a resposta terapêutica. Neste trabalho, avaliou-se a relação entre os fatores de risco e a terapêutica, resposta mais adequada, dados de maior relação com a estenose da anastomose bílio-entérica, período de surgimento, tempo de drenagem mais adequado, incidência de complicações, eficácia e segurança terapêutica. MÉTODOS: No período de março de 1993 a maio de 2006, foram avaliadas trinta e cinco pacientes com estenose da anastomose bílio-entérica após o transplante hepático prospectiva e retrospectivamente. Trinta e quatro (97,1%) tinham idade igual ou superior a um ano. Vinte e quatro (68%) tinham mais de 10 kg. Houve compatibilidade ABO em 100%, entre gêneros em 28,6% e na relação de peso entre receptor e doador em 71,4%. A principal indicação foi atresia de vias biliares e 45% dos transplantes foram realizados com doadores vivos. Trinta transplantes (86%) foram eletivos e 18 pacientes (51,4%) foram submetidos previamente à cirurgia de Kasai. A reconstrução biliar foi feita por meio da anastomose bílio-entérica em todos os pacientes. As estenoses foram confirmadas por colangiografia percutânea, dilatadas e drenadas. O calibre dos drenos foi aumentado nas reintervenções, sendo trocado a cada três meses e mantido por pelo menos seis meses. As complicações foram avaliadas e os pacientes foram distribuídos em grupos de resposta terapêutica de G1 a G4. RESULTADOS: Febre, icterícia, exame histopatológico demonstrando padrão obstrutivo biliar e dosagem elevada de gamaglutamiltransferase estiveram mais presentes no grupo com estenose. Os pacientes submetidos à cirurgia de Kasai apresentaram melhor resposta ao tratamento percutâneo (p = 0,05). As outras variáveis não demonstraram correlação estatisticamente significativa com a melhor ou pior resposta ao tratamento. Observou-se tempo médio de drenagem de 10 meses no grupo G1, onde houve menor ocorrência de complicações. CONCLUSÕES: Houve resposta satisfatória nos grupos com uma ou duas sessões (86%) de tratamento percutâneo. A cirurgia de Kasai se associa com melhores respostas ao tratamento; o exame histopatológico demonstrando padrão obstrutivo biliar e a elevação de gamaglutamiltransferase apresentam maior relação com a estenose, que ocorreu mais freqüentemente após o primeiro ano do transplante. Os pacientes drenados por mais de seis meses apresentaram melhores resultados. Entretanto, o prolongamento da drenagem associa-se com mais complicações. O tratamento percutâneo (dilatação e drenagem) é eficaz, seguro, com baixa taxa de complicações. / INTRODUCTION: Hepatic transplant is the chosen therapy for patients with advanced hepathopathy. Improvement on patients selection, surgical and immunologic advances increases the life expectancy. Biliary complications occur between 15 to 35% transplants and are associated to hepatic reduction techniques. The anastimotic stenosis occur between 5 to 14% and can be treated by surgery, endoscopic access or percutaneous. This last one presents fair results. However, it lacks of standard type, success criteria and consensus regarding to therapeutics response. Along this work, we evaluated the relation between risk factors and therapeutic, most adequate response, higher relation data of anastomotic bilioenteric stenosis, appearance period, most adequate time of drainage, incidence of complications, security and effectiveness therapeutic. METHODS: During the period of March 1993 to May 2006, 35 patients with anastomotic bilioenteric stenosis after having hepatic transplant prospective and retrospectively were evaluated. 34 of them (97.1%) were at the age of one year of above. 24 (68%) weighted more than 10kg. There was ABO compatibility in 100%, between genders in 28.6%, and 71.4% in relation to weight between receptor and donator. The main indication was biliary atresia ducts and 45% of transplants were made with living donators. 30 transplants (86%) were elective and 18 patients (51.4%) were previously submitted to Kasai surgery. The biliar reconstruction was made through anastomosis bilioenteric in all patients, The stenosis were confirmed by percutaneous colangiography, expanded and drained. The drain caliber was enlarged during the re-intervention, changed each 3 months and kept for at least 6 months. Complications were evaluated and the patients were allotted in groups according to G1 and G4 therapeutic response . RESULTS: fever, jaundice/icterus, hystopatologic exam with obstructed biliary pattern and high levels of gamaglutamitransferase were all presented in stenosis group. Patients submitted to Kasai surgery presented better response to the percutaneous treatment (p = 0.05). The other varieties did not demonstrate any statistically relevant association including better or worse response to the treatment. For group G1 were occurred less complications, 10 months of drainage was found as medium period. CONCLUSIONS: There was a satisfactory response in the groups with one or two sessions (86%) of percutaneous treatment. Kasai surgery is associated to the best responses to the treatment; hystopatologic exam with obstructed biliary pattern and elevation of gamaglutamitransferase presented better relation to stenosis, which have occurred more often after the first year of the transplant. Patients that have been drained for more than six months presented better results. However, the drainage extension is connected to more complications. The percutaneous treatment (expansion and drainage) is effective, with low complications rate.

Os objetivos do estudo foram avaliar as características clínicas das embolias arteriais sistêmicas no curso da endocardite infecciosa, a distribuição temporal, os fatores de risco de embolia e a influência prognóstica da embolia no curso da doença. Foram estudados 629 episódios de endocardite infecciosa. A idade dos pacientes variou de 2 meses a 83 anos (média 37,9 anos; desvio padrão 17,3). Ocorreram 396 (63%) episódios em homens e 233 (47%) em mulheres. Em 538 (85%) episódios, os pacientes eram portadores de doença cardíaca prévia, 272 (43%) com valvopatia, 224 (36%) portadores de prótese valvar cardíaca, 29 (5%) com doença cardíaca congênita, 13 (2%) com outras cardiopatias e 91 (14%) pacientes não apresentavam evidência de cardiopatia prévia. Os agentes etiológicos foram os estreptococos em 297 (47%) pacientes, os enterococos em 51 (8%), os Staphylococcus aureus em 77 (12,6%), os Staphylococcus epidermidis em 56 (9%), as bactérias gram-negativas em 33 (5%), os fungos em nove (1,4%), e outros microorganismos em 27 (4%). Em 79 (13%) pacientes as hemoculturas foram negativas. Os pacientes receberam tratamento clínico em 376 (60%) episódios e cirúrgico em 253 (40%). Para a análise estatística foram utilizados além da estatística descritiva, o método de Kaplan-Meier para avaliar a sobrevida livre de embolia e o prognóstico, comparadas com os testes de Log-rank e Breslow. Em seguida para a estimativa de riscos, foi ajustado o modelo de riscos proporcionais de Cox. As embolias arteriais ocorreram em 133 (21%) pacientes, cerebrais em 63 (47%), extracerebrais em 57 (43%) e cerebrais a extracerebrais em 13 (10%) pacientes. A distribuição temporal das embolias foi decrescente após o início dos sintomas. O risco de embolia não revelou diferença significativa quanto a idade, a sexo, o estado cardíaco, presença e número de vegetações identificadas no ecocardiograma e a modalidade de tratamento clínico ou cirúrgico. Os pacientes com endocardite causada por Staphylococcus aureus apresentaram risco de ocorrência de embolia 2,9 vezes maior do que os pacientes com endocardite causada por outros agentes etiológicos. Nos pacientes com endocardite infecciosa em prótese mitral e aórtica com vegetação identificada no ecocardiograma, o risco de embolia foi respectivamente 2,4 e 3,3 vezes maior relação aos pacientes com endocardite em valva natural ou em prótese sem vegetação. O risco de embolia foi menor a medida que o tempo decorrido entre o início dos sintomas e o tratamento aumentou. O risco de óbito nos pacientes que sofreram embolia duplicou em relação aos pacientes que não sofreram embolia. / The objectives of the study were to evaluate the clinical characteristics of systemic arterial embolism at infective endocarditis courses, the time related distribution of emboli, risk predictors and prognostic influence of emboli during active disease. So far, we studied 629 episodes of left-sided endocarditis. The patients were aged 37.9 ± 17.3 years; 396 (63%) episodes occurred in men; 233 (47%) in women; 538 (85%) episodes occurred in patients with heart disease: 272 (43%) had valvular heart disease, 224 (36%) had prosthetic heart valves, 29 (5%) had congenital heart disease, 13 (2%) had others cardiac diseases and 91 (14%) had no known heart disease. The causative microorganisms were streptococci in 297 (47%) patients, enterococci in 51 (8%), Staphylococcus aureus in 77 (1 2.6%), Sfaphylococcus epidermidis in 56 (9%), gram-negative bacteria in 33 (5%), fungi in nine (1.4%), and other microorganisms in 27 (4%); 79 (13%) patients had negative blood cultures. The treatment was medical in 376 (60%) and surgical in 253 (40%) episodes. Statistical analysis was pet-formed with descriptive analysis, with Kaplan-Meier methods to evaluate survival free of emboli and prognosis, and Cox proportional hazards model for risk analysis; 133 (21%) patients had an embolic event; 63 (47%) were cerebral emboli and 57 (43%) were extracerebral emboli and 13 (10%) were cerebral and extracerebral. The time-related distribution showed decrease in the incidence after beginning of symptoms. The risk for emboli was not significantly different relative to age, sex, cardiac status, presence or number of vegetations at echocardiogram, and medical or surgical treatment. The risk of emboli was 2.97 times higher in patients with Staphylacoccus aureus endocarditis. The risk of embolism in patients with infective endocarditis in mitral and aortic prosthetic valve with vegetations were 2.4 and 3.3 times higher. The risk of embolism decrease as the time elapsed between beginning of symptoms and treatment increased, suggesting a lower risk in less acute disease. Risk of death was 2.01 times higher in patients with embolism.

Le taux du diabète de type 2 (DT2) est en augmentation partout dans le monde, y compris dans les régions du monde où le trait drépanocytaire (TD) est très prévalent. Le TD, la forme hétérozygote de la drépanocytose, est généralement considéré comme bénin. Cependant, une dysfonction vasculaire plus importante a été récemment observée chez les patients DT2 porteurs du TD (DT2-TD) par rapport à des patients DT2 non-porteurs du TD. En outre, certaines études démontrent que le TD pourrait rendre le dépistage du DT2 plus complexe. De ce fait, les deux objectifs principaux de ma thèse étaient d’étudier les difficultés liées au dépistage et le suivi du DT2 chez les porteurs du TD, et d’évaluer les mécanismes et conséquences de la dysfonction vasculaire amplifiée chez les porteurs du TD. La 1ère étude a comparé deux mesures typiques (l’HbA1c et la glycémie à jeun) et une mesure atypique (fructosamine) de la glycémie chez des adultes sénégalais avec et sans le TD. Cette étude a démontré une disparité entre ces mesures qui étaient plus marquées chez des porteurs du TD. La 2ème étude a observé que les prévalences d’hypertension, de rétinopathie, et de néphropathie étaient plus élevées chez les sujets DT2-TD que chez les sujets diabétiques. La dysfonction vasculaire à l’origine de ces complications plus fréquentes semble impliquer les produits de glycation avancés. Les études 3 et 4 étaient réalisées dans un modèle murin du DT2-TD. L’étude 3 a montré une vasodilatation endothélium-dépendante significativement réduite chez des souris DT2-TD. Enfin, l’étude 4 a montré que la vasodilatation in-vivo induite par acétylcholine était augmentée chez la souris DT2-TD via un mécanisme dépendant de la cyclooxygenase-2. Ce travail de thèse a permis de mieux comprendre les difficultés liées au dépistage du DT2 chez les porteurs du TD, de montrer que le TD est un facteur de risque de complications vasculaire dans le DT2 et d’explorer les mécanismes à l’origine de cette dysfonction vasculaire plus marquée / Rates of type 2 diabetes (T2D) are rapidly increasing worldwide, including in regions, and among populations, of the globe where sickle cell trait (SCT) is prevalent. SCT, the heterozygote form of sickle cell disease, is generally considered a benign condition. However, evidence shows that vascular function is more severely impaired in people with combined T2D and SCT (T2D-SCT) than in those with T2D only. Furthermore, evidence suggests that SCT could complicate screening for T2D, thereby increasing the risk of delayed diagnosis of T2D. In light of this information, the main objectives of this thesis were to study the challenges related to diagnosing and monitoring T2D in individuals with SCT, and to evaluate the mechanisms and consequences of the amplified vascular dysfunction observed in T2D-SCT. Study 1 compared the agreement between two standard measures of glycemia, HbA1c and fasting glucose, and one alternative measure of glycemia, fructosamine, in Senegalese adults with and without SCT. The findings revealed substantial disparities between the markers of glycemia, and these differences were exaggerated in individuals with SCT. Study 2 illustrated that SCT could potentially augment the risk of developing retinopathy, nephropathy, and hypertension in T2D, and demonstrated that AGEs are likely implicated in the vascular dysfunction observed in T2D-SCT. Studies 3 and 4 studied microvascular function in a mouse model of T2D-SCT. Study 3 showed that T2D-SCT mice had significantly impaired endothelium-dependent vasodilation in-vivo. Study 4 revealed that ACH-mediated vasodilation in-vivo was significantly elevated in the microvasculature of mice with combined T2D and SCT due to cyclooxygenase-2 dependent mechanisms. Overall these findings deepen our understanding about the complexities related to diagnosing and managing T2D in individuals with SCT

OBJETIVO: Avaliar se as trombofilias pioram os desfechos maternos e fetais entre pacientes com formas graves de pré-eclâmpsia (PE). MÉTODO: De outubro/2009 a outubro/2014, foi realizada uma coorte retrospectiva de gestantes com PE grave diagnosticada antes de 34 semanas e seus recém-nascidos (RNs), internados no Hospital das Clínicas da FMUSP. Foram incluídas pacientes que tinham ausência de cardiopatias, nefropatias, diabetes pré-gestacional, moléstia trofoblástica gestacional, malformação fetal, gemelidade e que realizaram pesquisa de trombofilias no período pós-natal. Foram excluídas gestações subsequentes de uma mesma paciente no período de estudo, confirmação de alteração morfológica, genética ou cromossômica fetal, após o nascimento, e ainda as que realizaram uso de heparina ou ácido acetil salicílico durante a gestação. Foram pesquisados: fator V de Leiden, a mutação G20210A da protrombina, antitrombina, proteína C, proteína S, homocisteína, anticoagulante lúpico e anticorpos anticardiolipina IgG e IgM. Compararam-se os grupos com e sem trombofilia em relação a parâmetros clínicos e laboratoriais maternos e desfechos perinatais. Esta pesquisa foi aprovada pela Comissão de Ética para Análise de Projetos de Pesquisa da FMUSP. RESULTADOS: Entre as 127 pacientes selecionadas, 30 (23,6%) apresentaram diagnóstico de pelo menos uma trombofilia, hereditária ou adquirida. Entre as pacientes com trombofilia, tivemos mais pacientes da raça branca (p= 0,036). A análise de parâmetros maternos mostrou uma tendência das trombofílicas terem mais plaquetopenia (p=0,056) e evidenciou piora de parâmetros laboratoriais quando analisados em conjunto (aspartato aminotransferase >= 70 mg/dL, alanina aminotransferase>=70 mg/dL, plaquetas < 100.000/mm3, creatinina sérica >= 1,1 mg/dL); p=0,017. Não houve diferença quanto aos achados perinatais fetais. CONCLUSÃO: A presença de trombofilia associa-se à piora em parâmetros laboratoriais maternos, em pacientes com formas graves de PE, sem, contudo, piorar os desfechos perinatais, ao menos na amostra estudada / OBJECTIVE: To evaluate whether thrombophilia worsens maternal and foetal outcomes among patients with severe preeclampsia (PE). METHOD: From October 2009 to October 2014, a retrospective cohort study was performed on pregnant women with severe PE diagnosed before 34 weeks of gestation and their newborns hospitalized at the Clinics Hospital, FMUSP. Patients who had no heart disease, nephropathies, pre-gestational diabetes, gestational trophoblastic disease, foetal malformation, or twin pregnancy and who underwent thrombophilia screening during the postnatal period were included. Subsequent pregnancies of the same patient during the study period; cases of foetal morphological, genetic, or chromosomal abnormalities after birth; and women who used heparin or acetylsalicylic acid during pregnancy were excluded. Factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C, protein S, homocysteine, lupus anticoagulant, and anticardiolipin IgG and IgM antibodies were analysed. The groups with and without thrombophilia were compared regarding their maternal clinical and laboratory parameters and perinatal outcomes. This research was approved by the Ethics Committee for the Analysis of Research Projects of FMUSP. RESULTS: Of the 127 patients selected, 30 (23.6%) had a diagnosis of at least one thrombophilia, either hereditary or acquired. Among the patients with thrombophilia, we observed more white patients (p = 0.036). Analysis of maternal parameters showed a tendency of thrombophilic women to have more thrombocytopenia (p = 0.056) and showed worsening of laboratory parameters when analysed jointly (aspartate aminotransferase >= 70 mg/dL, alanine aminotransferase >= 70 mg/dL, platelets < 100,000/mm3, serum creatinine >= 1.1 mg/dL; p = 0.017). There were no differences in foetal perinatal findings. CONCLUSION: The presence of thrombophilia is associated with worsening of maternal laboratory parameters in patients with severe forms of PE but not with the worsening of perinatal outcomes, at least in the sample studied

OBJETIVO: Avaliar se as trombofilias pioram os desfechos maternos e fetais entre pacientes com formas graves de pré-eclâmpsia (PE). MÉTODO: De outubro/2009 a outubro/2014, foi realizada uma coorte retrospectiva de gestantes com PE grave diagnosticada antes de 34 semanas e seus recém-nascidos (RNs), internados no Hospital das Clínicas da FMUSP. Foram incluídas pacientes que tinham ausência de cardiopatias, nefropatias, diabetes pré-gestacional, moléstia trofoblástica gestacional, malformação fetal, gemelidade e que realizaram pesquisa de trombofilias no período pós-natal. Foram excluídas gestações subsequentes de uma mesma paciente no período de estudo, confirmação de alteração morfológica, genética ou cromossômica fetal, após o nascimento, e ainda as que realizaram uso de heparina ou ácido acetil salicílico durante a gestação. Foram pesquisados: fator V de Leiden, a mutação G20210A da protrombina, antitrombina, proteína C, proteína S, homocisteína, anticoagulante lúpico e anticorpos anticardiolipina IgG e IgM. Compararam-se os grupos com e sem trombofilia em relação a parâmetros clínicos e laboratoriais maternos e desfechos perinatais. Esta pesquisa foi aprovada pela Comissão de Ética para Análise de Projetos de Pesquisa da FMUSP. RESULTADOS: Entre as 127 pacientes selecionadas, 30 (23,6%) apresentaram diagnóstico de pelo menos uma trombofilia, hereditária ou adquirida. Entre as pacientes com trombofilia, tivemos mais pacientes da raça branca (p= 0,036). A análise de parâmetros maternos mostrou uma tendência das trombofílicas terem mais plaquetopenia (p=0,056) e evidenciou piora de parâmetros laboratoriais quando analisados em conjunto (aspartato aminotransferase >= 70 mg/dL, alanina aminotransferase>=70 mg/dL, plaquetas < 100.000/mm3, creatinina sérica >= 1,1 mg/dL); p=0,017. Não houve diferença quanto aos achados perinatais fetais. CONCLUSÃO: A presença de trombofilia associa-se à piora em parâmetros laboratoriais maternos, em pacientes com formas graves de PE, sem, contudo, piorar os desfechos perinatais, ao menos na amostra estudada / OBJECTIVE: To evaluate whether thrombophilia worsens maternal and foetal outcomes among patients with severe preeclampsia (PE). METHOD: From October 2009 to October 2014, a retrospective cohort study was performed on pregnant women with severe PE diagnosed before 34 weeks of gestation and their newborns hospitalized at the Clinics Hospital, FMUSP. Patients who had no heart disease, nephropathies, pre-gestational diabetes, gestational trophoblastic disease, foetal malformation, or twin pregnancy and who underwent thrombophilia screening during the postnatal period were included. Subsequent pregnancies of the same patient during the study period; cases of foetal morphological, genetic, or chromosomal abnormalities after birth; and women who used heparin or acetylsalicylic acid during pregnancy were excluded. Factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C, protein S, homocysteine, lupus anticoagulant, and anticardiolipin IgG and IgM antibodies were analysed. The groups with and without thrombophilia were compared regarding their maternal clinical and laboratory parameters and perinatal outcomes. This research was approved by the Ethics Committee for the Analysis of Research Projects of FMUSP. RESULTS: Of the 127 patients selected, 30 (23.6%) had a diagnosis of at least one thrombophilia, either hereditary or acquired. Among the patients with thrombophilia, we observed more white patients (p = 0.036). Analysis of maternal parameters showed a tendency of thrombophilic women to have more thrombocytopenia (p = 0.056) and showed worsening of laboratory parameters when analysed jointly (aspartate aminotransferase >= 70 mg/dL, alanine aminotransferase >= 70 mg/dL, platelets < 100,000/mm3, serum creatinine >= 1.1 mg/dL; p = 0.017). There were no differences in foetal perinatal findings. CONCLUSION: The presence of thrombophilia is associated with worsening of maternal laboratory parameters in patients with severe forms of PE but not with the worsening of perinatal outcomes, at least in the sample studied

Cardiac remodeling after acute myocardial infarction (MI) is an important process that leads to progressive ventricular enlargement and heart failure. Several variables have been identified to predict an increase in left ventricular (LV) volume and a decrease of LV ejection fraction (LVEF) after an acute MI including infarct size, anterior location, cardiac enzyme level, transmurality of the infarct, patency of the infarct-related artery, end systolic volume (ESV) and mitral deceleration time, etc. / Regional disturbances of LV wall motion have long been recognized to occur in patients with cardiac diseases, such as hypertrophic cardiomyopathy, unstable angina, acute ischemia, and MI. Tissue Doppler imaging (TDI) is recently established for detecting regional contractile abnormalities and asynchrony, and can predict reverse remodeling and improved synchronicity after biventricular pacing therapy in heart failure patients. However, it is unclear whether LV asynchrony plays an important role in the evolutionary changes of LV remodeling after an acute infarction and whether it can predict the changes independently. / The identification of transmural extent of myocardial necrosis and degree of non-viability after acute MI is clinically important. TDI-derived strain rate imaging (SRI) quantifies local rate of myocardial deformation and has the potential to differentiate viable from infarcted myocardium. / Therefore, in this study we aimed to investigate: (1) Whether SRI may differentiate transmural from non-transmural MI as assessed by ce-MRI in routine patients post acute infarction, and establish practical cutoff values for identifying transmural scar tissue from non-transmural or subendocardial infarction with viable myocardium. (2) Whether LV systolic and diastolic asynchrony measured by TDI occurs early after acute MI even in the absence of widening of QRS complexes, and determine if this is explained by the site and extent of the infarction measured by ce-MRI. (3) The relationships between serial measurements of infarct size on ce-MRI and LV remodeling process after an acute infarction, and determine whether early assessment of infarct size predicts progressive ventricular enlargement and cardiac dysfunction, and whether it differs with infarct location. (4) The relationships between LV asynchrony, infarct size and LV remodeling, and determine whether early assessment of LV asynchrony by TDI compared with standard clinical correlates of LV remodeling and infarct size predicts progressive ventricular enlargement and cardiac dysfunction. (Abstract shortened by UMI.) / Zhang Yan. / "April 2005." / Adviser: John E. Sanderson. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0175. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 161-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.